Phylogenetic analysis, morphological studies, element profiling, and muscarine detection reveal a new toxic Inosperma (Inocybaceae, Agaricales) species from tropical China.

Tropical Asian collections of Inosperma are usually poisonous mushrooms that have caused many poisoning incidents. However, the species diversity and the toxic mechanisms of these Inosperma species are still unclear. In this study, we describe the discovery of Inosperma wuzhishanense sp. nov. from Wuzhishan City, Hainan Province, tropical China. The new species was identified based on morphological and multi-locus (ITS, nrLSU, and RPB2) phylogenetic analyses. The new species is characterized by its reddish-brown pileus, fibrillose stipes with finely protruding fibrils, rather crowded lamellae, smooth and ellipsoid basidiospores, and mostly clavate, thin-walled cheilocystidia. The new species is phylogenetically nested in the Old World tropical clade 2 and is sister to the tropical Indian taxa I. akirnum. Detailed descriptions, color photos of the new species, and comparisons with its closely related species are provided. Additionally, the muscarine content of the new species was analyzed by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). The muscarine contents ranged from 4,359.79 ± 83.87 mg/kg to 7,114.03 ± 76.55 mg/kg, 2,748.37 ± 106.85 mg/kg to 4,491.35 ± 467.21 mg/kg, and 2,301.36 ± 83.52 mg/kg to 2,775.90 ± 205.624 mg/kg in the stipe, pileus, and lamellae, respectively. The elemental composition and concentration were determined using inductively coupled plasma-mass spectrometry (ICP-MS). A total of 24 elements were detected. Among the heavy metals detected, arsenic showed the highest level of toxicity with a concentration of 36.76 ± 0.43 mg/kg.

Insights into the mechanisms of triptolide nephrotoxicity through network pharmacology-based analysis and RNA-seq.

Introduction: Triptolide (TPL) is a promising plant-derived compound for clinical therapy of multiple human diseases; however, its application was limited considering its toxicity. Methods: To explore the underlying molecular mechanism of TPL nephrotoxicity, a network pharmacology based approach was utilized to predict candidate targets related with TPL toxicity, followed by deep RNA-seq analysis to characterize the features of three transcriptional elements include protein coding genes (PCGs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) as well as their associations with nephrotoxicity in rats with TPL treatment. Results & Discussion: Although the deeper mechanisms of TPL nephrotoxcity remain further exploration, our results suggested that c-Jun is a potential target of TPL and Per1 related circadian rhythm signaling is involved in TPL induced renal toxicity.

Sarcomatoid intrahepatic cholangiocarcinoma mimicking liver abscess: A case report.

BACKGROUND: Sarcomatoid intrahepatic cholangiocarcinoma (SICC) is an extremely rare and highly invasive malignant tumor of the liver. To our knowledge, the imaging findings of sarcomatous cholangiocarcinoma have been rarely reported; and radiological features of this tumor mimicking liver abscess have not yet been reported. CASE SUMMARY: We present a case of SICC mimicking liver abscess. The patient, a 43-year-old male, complained of repeated upper right abdominal discomfort and intermittent distension over a period of one month. Radiology examination revealed a huge focal lesion in the right liver. The lesion was hypointense on computed tomography with honeycomb enhancement surrounded by enhanced peripheral areas. It showed a hypo-signal on non-contrast T1-weighted images and a hyper-signal on non-contrast T2-weighted images. Radiologists diagnosed the lesion as an atypical liver abscess. The patient underwent a hepatectomy. After surgery, he survived another 2.5 mo before passing away. A search of PubMed and Google revealed 43 non-repeated cases of SICC reported in 20 published studies. The following is a short review in order to improve the diagnostic and therapeutic skills in cases of SICC. CONCLUSION: This report presents the clinical and radiological features of SICC and imaging features which showed hypovascularity and progressive enhancement. SICC can present as a multilocular cyst on radiological images and it is necessary to distinguish this lesion from an atypical abscess. Simple surgical treatment is not the best treatment option for this disease.

Undifferentiated myxoid lipoblastoma with PLAG1 gene rearrangement in infant.

OBJECTIVES: To analyze the clinicopathologic feature, diagnosis and differential diagnosis of undifferentiated myxoid lipoblastoma in infant. METHODS: The study included 2 cases of undifferentiated myxoid lipoblastoma in infant according to the molecular genetic diagnosis. The relevant clinicopathologic feature was investigated. RESULTS: We describe 2 cases of undifferentiated myxoid lipoblastoma in infant. The both large circumscribed masses are located in deep soft tissue. Unlike most lipoblastoma, lobulated appearance was not obvious in one case and completely absent in another. The both cases presented prominent myxoid change with a plexiform vascular pattern. There were some spindle-shaped or stellate mesenchymal cells, while no any mature adipocytes. The initial suggestion of case 1 was myxoid liposarcoma, and case 2 was aggressive angiomyxoma. However, few S-100 positive lipoblasts suggested the origin of the tumor. FISH analysis using a PLAG1 break apart probe confirmed a PLAG1 rearrangment. The final diagnosis was undifferentiated myxoid lipoblastoma. CONCLUSIONS: The undifferentiated myxoid lipoblastoma is a very rare tumor in infant. Histologically, prominent myxoid change, a plexiform vascular pattern and lacking of mature adipocytes make it indistinguishable from myxoid liposarcoma, PMMTI and aggressive angiomyxoma. The S-100 positive lipoblasts and genetic rearrangement of PLAG1 helps in confirming the diagnosis. Even if there were no mature adipocytes, myxoid lipoblastoma was still a diagnosis that can not be ignored in myxoid tumors in children.

Characterization of breast lesions using diffusion kurtosis model-based imaging: An initial experience.

OBJECTIVE: To investigate the characterization of breast lesions using diffusion kurtosis model-based imaging. METHODS: This prospective study included 120 consecutive patients underwent preoperative DCE-MRI examinations and multi-b-value diffusion-weighted imaging (DWI). Among them, 88 malignant lesions and 44 benign lesions were detected, 56 normal fibroglandular breast tissue were selected as normal control. Conventional apparent diffusion coefficient (ADC), DKI-based parameters mean kurtosis (MK) and mean diffusivity (MD) were analyzed by lesions types and histological subtypes using one-way ANOVA and receiver operating characteristic (ROC) curve. RESULTS: (1) The malignant group showed significantly lower ADC and MD (1.07±0.32×10-3 mm2/s and 1.30±0.40×10-3 mm2/s, respectively) and higher MK (0.87±0.18) than those in the benign group (1.29±0.26×10-3 mm2/s, 1.62±0.31×10-3 mm2/s and 0.67±0.18) and control group (1.67±0.33×10-3 mm2/s, 2.24±0.28×10-3 mm2/s and 0.52±0.08) with all P < 0.001. (2) Areas under ROC curve (AUC) for diagnosing malignant lesions were 0.936 for MD, 0.911 for MK and 0.897 for ADC, respectively. AUC for MD was significantly higher than that for ADC (P = 0.015). The optimal cut-off value, sensitivity, specificity, positive predictive value, negative predictive value and accuracy were as follow: ADC = 1.18×10-3mm2/s, 78.3%, 93.2%, 81.2%, 81.6%, 81.4%; MD = 1.48×10-3mm2/s, 82.2%, 98.3%, 84.4%, 87.8%, 86.2%; MK = 0.78, 91.5%, 85.3%, 89.0%, 85.8%, 87.2%. (3) Invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS) and mucinous adenocarcinoma also showed significant differences among ADC, MD and MK (with P < 0.05). CONCLUSIONS: MR-DKI parameters enable to improve breast lesion characterization and have diagnostic potential applying to different pathological subtypes of breast cancers.

Evaluation of the MiSeq FGx system for use in forensic casework.

Capillary electrophoresis (CE) is widely used in forensic genetics to study short tandem repeats (STRs). Recently, next-generation sequencing (NGS) platforms have facilitated the development of new strategies for forensic DNA typing. Several studies have shown that NGS successfully analyzes challenging samples. However, because NGS is complicated and time-consuming, it remains unclear whether NGS platforms offer significant advantages over CE for all forensic cases. Here, the MiSeq FGx system was used to test some cases that had previously been analyzed using CE. These cases included paternity test cases in which some samples exhibited locus inconsistencies; samples with off-ladder (OL) alleles; samples with triallelic patterns; and samples with amelogenin test abnormalities. The results generated by MiSeq FGx were compared to those previously generated by CE. The MiSeq FGx and CE results were consistent with the exception of three samples, where inconsistencies were observed at the Penta D locus. For all three incongruent samples, the MiSeq FGx results were correct. Sequence analysis indicated that, in two cases, mismatches were due to undetected alleles rather than mutations. In two additional cases, mutation sources were identified, and in a fifth case, mutation step size was reconsidered. MiSeq FGx was used to identify OL alleles and samples with amelogenin test abnormalities. For cases where verification was required via CE analysis, the simultaneous NGS amplification of several types of multiple genetic markers improved testing efficiency. In addition, we identified additional sequence variants at autosomal, Y chromosomal, and X chromosomal STR loci in the Han Chinese population from northern China. Our results will be useful for future forensic analyses of STR genotypes in Chinese populations. It is likely that NGS would be more widely used in forensic genetics if costs and procedure complexity were reduced.

Association of leptin, visfatin, apelin, resistin and adiponectin with clear cell renal cell carcinoma.

Although an association between obesity and the occurrence of renal cell carcinoma (RCC) has been identified, the mechanism by which obesity functions to increase this risk of cancer remains unclear. Leptin, visfatin, apelin, resistin and adiponectin are peptide hormones secreted by adipocytes; it is considered that these may affect RCC development by exerting effects on proliferation, cell growth and inflammation. The aim of the present study was to investigate the association between the aforementioned adipokine genes and clear cell RCC (CC-RCC). The GSE6344 dataset was downloaded from the Gene Expression Omnibus database, and the relative expression levels of the adipokine genes were analyzed. To verify the results of the mRNA microarray, 77 paired samples of CC-RCC and corresponding adjacent normal tissue were allocated into two groups. The extraction of total RNA was conducted, and the mRNA expression of adipokine genes was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The data from the GSE6344 dataset indicated that the expression of visfatin and apelin was upregulated (P<0.0001 and P<0.01, respectively), and adiponectin was downregulated (P<0.001) in the CC-RCC tissues compared with the adjacent normal tissues. The data from RT-qPCR demonstrated that visfatin and resistin gene expression was increased (P<0.01 and P<0.05, respectively) in the CC-RCC tissues. Furthermore, the mRNA expression level of leptin and adiponectin in the adjacent normal tissue was higher than those in the cancer tissue (P<0.01). The current study verifies that visfatin and adiponectin are associated with an increased risk of CC-RCC, which presents further insights into the molecular mechanisms of CC-RCC tumorigenesis.

High-resolution Melting PCR Analysis for Genotyping Lys109Arg and Gln223Arg in Patients with Renal Cell Carcinoma.

Although several studies have documented the role of leptin receptor gene polymorphisms in cancers, the association between leptin receptor gene polymorphisms and renal cell carcinoma (RCC) remains unknown. The aim of this study was to develop a high-resolution melting (HRM) approach for genotyping single nucleotide polymorphisms of leptin receptor gene on the LightCycler 480, and to explore the relation between polymorphisms of the leptin receptor gene and RCC. The study population consisted of 83 patients with renal cell carcinoma and 161 healthy control subjects. The Lys109Arg (A/G) and Gln223Arg (A/G) polymorphisms of leptin receptor gene were examined with HRM assay. Direct DNA sequencing and PCR-restriction fragment length polymorphisms were used as a reference method for genotyping Lys109Arg and Gln223Arg, respectively. Three genotypes of Lys109Arg or Gln223Arg were clearly distinguishable from the melting curve shapes with HRM assay. The data also showed the results of the direct DNA sequencing or PCR-restriction fragment length polymorphisms analysis were in complete concordance to genotyping results obtained by HRM (kappa=1.0). In addition, the data showed the G-G haplotype frequency was higher (p<0.05), and that the A-G (p<0.001) and G-A (p<0.01) haplotypes frequencies were lower in the RCC than controls. We developed a rapid, low cost, high-throughput and reliable single-tube technology for genotyping Lys109Arg and Gln223Arg polymorphisms. In addition, our data suggest that Lys109Arg and Gln223Arg gene polymorphisms are associated with RCC in Chinese Han studied population.

Risk factors for depth of infiltration in the differentiated depressed early gastric carcinoma: a preliminary analysis.

BACKGROUND: To analyze the clinicopathologic factors associated with mucosal and submucosal infiltration in differentiated depressed early gastric cancer, and screening factors that can predict depth of infiltration before endoscopic treatment. METHODS: The study included 35 cases of mucosal carcinomas and 66 cases of submucosal carcinomas according to the pathological diagnosis. The relevant clinicopathologic factors were investigated by univariate and multivariate analysis. RESULTS: The average depth of the depressed lesions for the submucosal group was significantly more than that for the mucosal group. The proportion of the lesions with rough bottom surface and abnormal surrounding folds was significantly higher in the submucosal group compared to that in the mucosal group. Logistic regression analysis indicated that the above-mentioned three factors were independent risk factors that could be used to predict mucosal and submucosal infiltration. Area under the curve (AUC) of receiver operating characteristic (ROC) of the ordinal above-mentioned three factors for predicting submucosal infiltration was 0.716, 0.663, 0.704, respectively. Stratified analysis showed that the 100% cases with lesion depth ≥ 2.5 mm and rough bottom surface developed submucosal infiltration regardless of the morphological changes of the folds. CONCLUSION: The study identified independent risk factors for predicting mucosal and submucosal infiltration in depressed differentiated early gastric cancer, which may evaluate the degree of penetration before endoscopic treatment. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_206.

Association of leptin receptor Lys109Arg and Gln223Arg polymorphisms with increased risk of clear cell renal cell carcinoma.

BACKGROUND: Although roles of genetic polymorphisms of leptin receptor (LEPR) gene in several cancers have been documented, the association between polymorphisms of LEPR and clear cell renal cell carcinoma (CC-RCC) remains unknown. The aim of this study was to explore any relation. MATERIALS AND METHODS: The study population consisted of 77 patients with CC-RCC and 161 healthy control subjects. Polymorphism analyses of Lys109Arg and Gln223Arg were performed by direct DNA sequencing and PCR-restriction fragment length polymorphism approaches respectively. RESULTS: Comparisons of allelic and genotypic frequencies in Lys109Arg and Gln223Arg showed no significant difference between the cases and controls. However, when evaluating the combined genotype of Lys109Arg and Gln223Arg, risk with GG/GG was increased (OR=1.85, 95%CI=1.04-3.30) and with GA/GG or GG/GA was decreased (OR=0.07, 95%CI=0.01-0.54; OR and 95%CI of the latter could not be calculated for a value of zero) . Furthermore, the G-G haplotype frequency of Lys109Arg and Gln223Arg in the cases was higher (OR=1.68; 95%CI=1.02-2.76). In contrast, the A-G and G-A haplotype frequencies in the cases were lower than those in the controls (OR=0.06; 95%CI=0.01 to 0.47; OR and 95%CI of the latter could not be calculated for a value of zero). In addition, the Lys109Arg A allele was in LD with the Gln223Arg A allele (d'=0.9399) in the CC-RCC subjects, but not in the controls. CONCLUSIONS: Our data suggest that the GG/GG combined genotype and G-G haplotype of Lys109Arg and Gln223Arg can act as evaluating factors for CC-RCC risk.

Decreased analgesic effect of morphine, but not buprenorphine, in patients with advanced P-glycoprotein(+) cancers.

BACKGROUND: P-glycoprotein (P-gp) is expressed on the blood-brain barrier (BBB) and acts as a transporter regulating the analgesic effect of morphine. The P-gp is also expressed by different types of tumors. The aim of this study was to determine the potential association of the P-gp expression in malignant tumors with analgesic effects in patients. METHODS: The P-gp expression in 120 malignant tumors was examined by immunohistochemistry. The analgesic responses of individual patients to morphine and buprenorphine (BNP) were evaluated by visual analog scale (VAS). The levels of plasma morphine and BNP were determined by HPLC. RESULTS: We found that there was no significant difference in the values of VAS between patients with P-gp(+) and P-gp(-) malignant tumors in responses to 0.000025 g x kg(-2) of BNP administered by patient-controlled intravenous analgesia (PCIA), accompanied by similar levels of plasma BNP in those patients. In contrast, the values of VAS in response to 0.00075 g x kg(-2) of morphine in patients with P-gp(+) tumors were significantly greater than those in the patients with P-gp(-) tumors, although similar levels of plasma morphine were detected in both groups of patients. Furthermore, treatment with a higher dose (0.0011 g x kg(-2)) of morphine effectively controlled pain in those with P-gp(+) tumors. CONCLUSION: Our data indicated that patients with P-gp(+) tumors required a higher dose of morphine to achieve an analgesic effect and that the P-gp expression in tumors may be valuable for predicting the analgesic responses of patients with severe pain to morphine.

[Clinicopathological analysis of sudden cardiac death cases by autopsy].

OBJECTIVE: To explore the major correlation factors and cardiac pathological changes of sudden cardiac death (SCD). METHODS: The clinical and pathological profiles of 119 SCD cases at Wuxi People's Hospital Affiliated to Nanjing Medical University from January 1985 to March 2012 were retrospectively analyzed. And the parameters of gender, age, causes of death and pathological changes of SCD were included. RESULTS: Among them, the primary etiologies were coronary atherosclerotic heart disease (n = 53, 44.5%), hypertensive heart disease (n = 9, 7.6%), myocarditis (n = 13, 10.9%), acute pulmonary embolism (n = 8, 6.7%) and myocardiopathy(n = 3, 2.5%). The heart weights of male and female cases were (407 ± 126) and (349 ± 101) g respectively. Among 53 cases of coronary heart disease, there were 28 cases (52.8%) of grade IV coronary artery atherosclerotic stenosis and 17 were involved with multiple branches. The differences of coronary artery stenosis were insignificant between gender and age (P > 0.05). Acute myocardial infarction occurred in 18 cases and 15 of them were complicated with old myocardial infarction (OMI) while there were 27 cases of simple OMI. Twenty cases (16.8%) without obvious cardiac organic pathological changes were classified as juvenile sudden unexplained death. CONCLUSIONS: Sudden and dangerous SCD frequently occurs in elders. Multiple severe coronary atherosclerotic stenosis is an important pathological hallmark of SCD.

Interdigitating dendritic cell tumor of the lymph node in the right submaxillary region: a case report and review of the literature.

Interdigitating dendritic cell tumor/sarcoma is an extremely rare neoplasm that mainly occurs in the lymph node, with only 51 cases reported in the literature to date. The authors report the case of a 41-year-old woman who presented with a 4-month history of a gradually enlarging painless mobile lymphadenopathy in the right submaxillary region. The lymph node mass was completely resected and was treated with 1 cycle of CHOP chemotherapy. After 10 months, she was alive with no evidence of disease. Because interdigitating dendritic cell sarcomas are rare and can show morphologic and immunohistochemical heterogeneity, correct diagnosis requires a high index of suspicion and complete pathological study.

Giant-cell anaplastic carcinoma with osteoclastic giant cells of the chest cavity: a distinctive form of thymic carcinoma?

Here, the authors describe a case of giant-cell anaplastic carcinoma with osteoclastic giant cells of the chest cavity-which could be a distinctive form of thymic carcinoma-which expressed CD5 and CD45. To the authors' knowledge, there has been no previous report on this subject. A 62-year-old woman presented with continuous pain in the left back associated with coughing and shortness of breath for more than 2 months prior to referral to the hospital. Palliative resection of a mediastinal tumor was performed. During the operation, it was found that the mass occupied most of the chest invading the chest wall, aorta, vena cava, and lung tissue. The patient soon died from diabetic complications in spite of anti-infection treatment. The tumor was composed of large areas of necrosis and anaplastic neoplastic giant cells with high mitotic activity, and osteoclast-like cells; there was marked inflammatory cell infiltration. The anaplastic neoplastic giant cells were immunoreactive for CKpan, CD5, CD45, VIM, and p53. Approximately 50% to 60% of the tumor cells showed immunoreactivity for Ki-67. In situ hybridization for Epstein-Barr virus-encoded RNA was negative for tumor cells and nonneoplastic osteoclastic giant cells. Because this tumor is very rare, extensive clinical, radiological, and morphological examinations as well as immunohistochemical studies are essential to make the diagnosis.

The expression and clinical significance of TGF-beta1 and MMP2 in human renal clear cell carcinoma.

The expression and clinical significance of transforming growth factor beta1 (TGF-beta1) and matrix metalloproteinase-2 (MMP2) in human renal clear cell carcinoma (RCCC) were investigated. The intensity of TGF-beta1 and MMP2 expression in RCCC kidneys was significantly higher than that in normal kidneys. Expression of TGF-beta1 and MMP2 in RCCC tissues was positively correlated with pathological grade and clinical stage. There was also a significant correlation between TGF-beta1 and Msshese analyses indicate that upregulation of TGF-beta1 and MMP2 expression may occur during the progression of RCCC. Thus, TGF-beta1 and MMP2 may be useful molecular markers for evaluating prognosis in RCCC patients.